Antitumor enzyme: polyethylene glycol-modified asparaginase.
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Adolescent↗
Biomedical subjects
Y Inada
Publications and source records attributed to Y Inada.
Activation of kallikrein-kinin system in human plasma with purified serine protease from Dermatophagoides farinae.
An aqueous extract from a mite culture, of Dermatophagoides farinae, activated prekallikrein to kallikrein in normal plasma. Crude protein preparation, obtained by ammonium sulfate precipitation (95% saturation) from the extract, exhibited high activity (0.81 units/mg protein) towards a synthetic substrate of coagulation factor XIIa, Boc-Gln-Gly-Arg-MCA, and had also activity to form kallikrein in human plasma deficient in coagulation factor XII. Treatment of the protein preparation with phenylmethylsulfonyl fluoride (PMSF), an inhibitor of serine enzyme, gave rise to inactivation of both activities. Thus, the serine protease specific for Boc-Gln-Gly-Arg-MCA in mite cultures of D. farinae was purified by ammonium sulfate precipitation and chromatographies on p-aminobenzamidine-sepharose CL-4B, DEAE-Toyopearl 650M, Sephadex G-75 superfine and Sephacryl S-200. The purified protease was homogeneous electrophoretically, and its molecular weight was estimated to be 30,000. The optimum pH and temperature were around 7.5 and 50 degrees C, respectively. The specific activity was 36 units/mg protein at pH 7.4 and 37 degrees C. The activity was completely inhibited by PMSF. The serine protease had the activity to activate the kallikrein-kinin system in normal human plasma.
Animals↗
Antagonistic action of AA-2414 on thromboxane A2/prostaglandin endoperoxide receptor in platelets and blood vessels.
AA-2414, (+/-)-7-(3,5,6-trimethyl-1,4-benzoquinon-2-yl)-7-phenylheptanoi c acid, inhibited the aggregation of guinea pig platelets induced by a prostaglandin endoperoxide (PGH2) analogue, U-44069 and the specific binding of another analogue, [3H]U-46619 to washed guinea pig platelets with IC50 values of 3.1 x 10(-7) and 8.2 x 10(-9) M, respectively. AA-2414 competitively inhibited the contraction of rabbit aorta and pig coronary arteries induced by U-44069 with pA2 values of 8.3 and 9.0, respectively. AA-2414 also inhibited the contraction of rabbit aorta induced by PGF2 alpha (pA2: 7.8) and the contraction of pig coronary arteries induced by PGF2 alpha, PGD2 and 9 alpha,11 beta-PGF2 with pA2 values of 7.8, 8.6 and 7.8, respectively. But, AA-2414 had no effect on the antiaggregatory effect of PGD2 on the aggregation of guinea pig platelets. In experiments with guinea pigs ex vivo, AA-2414 (0.1-1 mg/kg, p.o.) dose-dependently inhibited the platelet aggregation induced by U-44069; the inhibition at a dose of 1 mg/kg was 100% at 1 hr and was 89% even at 24 hr after the administration. The thromboxane (TX) A2/PGH2 receptor antagonistic action of AA-2414 was stereospecific. These results show that AA-2414 is a potent, orally active and long acting TXA2/PGH2 receptor antagonist. In addition, AA-2414 has PGF2 alpha, PGD2 and 9 alpha,11 beta-PGF2 antagonistic effects.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
Indications for surgical treatment of putaminal hemorrhage. Comparative study based on serial CT and time-course analysis.
Serial computerized tomography (CT) scans were correlated with a precise time-course analysis of the neurological condition of 180 patients with hypertensive putaminal hemorrhage. All patients entered the study within 3 hours of the ictus. In this series, 111 patients were treated conservatively and 69 surgically. The neurological condition of each patient was measured by means of a newly proposed grading system for intracerebral hemorrhage-intracranial hemorrhage (ICH grade) which is a modification of the Glasgow Coma Scale. Serial CT scans revealed that most hemorrhages were completed within 6 hours after ictus. Based on the ICH grade at 6 hours postictus, a clinical classification of the severity of putaminal hemorrhage was defined: fulminant, rapidly progressive, slowly progressive, and nonprogressive. According to this classification, precise time courses of the ICH grade were compared between the conservative and surgical treatment groups in a 7-day postictal period. Activities of daily living at 6 months after ictus were also compared. Surgical treatment for a rapidly progressive hemorrhage appears to be beneficial if undertaken in patients under 65 years of age. Surgery in a slowly progressive hemorrhage should be considered only in a small number of patients who deteriorate neurologically with conservative treatment. In this series of patients, surgical treatment of fulminant and nonprogressive hemorrhage was not likely to improve the quality of life or functional recovery. Regardless of treatment modality, CT provided evidence that patients with anterior capsular hemorrhage (16% in this series) showed good recovery of motor and speech function.
Activities of Daily Living↗
[A clinical evaluation of distant metastases from a hepatocellular carcinoma with reference to location, frequency, symptoms, treatment & prognosis].
A clinical analysis of patients with hepatocellular carcinoma (HCC) associated with a distant metastases has been undertaken by the authors. Studied were eight patients (Group A) whose distant metastases were detected at the time of their initial examination, and 24 patients (Group B) whose distant metastases had been diagnosed during the course of treatment of their primary lesions. Complications arising from liver cirrhosis in Group A was less than in Group B. The location of the metastases were the bone in 16, the lung and the adrenal gland in four, the brain and the skin in two and the kidney in one. The mean survival times were 4.6 months (Group A), and 6.3 months (Group B). The cause of death was chiefly a progression of the primary lesion, except for one brain metastases. This analysis had shown that treatment of a bone metastasis is necessary for the relief of pain, and that care should be taken for the prevention of a fracture or paralysis, and that control of the primary lesion is necessary for improving the chances of survival.
Adrenal Gland Neoplasms↗
[Chemical modification of proteins with polyethylene glycol (PEG): approach to new protein drugs].
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Adjuvants, Pharmaceutic↗
[Hemodynamic features of hypotension induced by nicardipine in dogs].
Hemodynamic features of hypotension induced by nicardipine were studied in 18 mongrel dogs under 0.87% halothane in oxygen (1MAC). They were randomly allocated to one of two groups. Group C received no vasodilator therapy and served as control and group N received infusion of nicardipine. Mean arterial pressure decreased and was maintained at 60 mmHg for 60 minutes in group N. No change was noted in hemodynamic variables measured in group C throughout the experiment. During and after induced hypotension in group N, cardiac index (CI), stroke volume index (SVI), central venous pressure (CVP), and right ventricular stroke work index (RVSWI) increased significantly compared with the control values. On the other hand, systemic vascular resistance (SVR) was significantly reduced, reaching 25% of the control value at the end of hypotension period. Heart rate showed a progressive increase but not significantly. Left ventricular maximum dp/dt showed a moderate increase during hypotension, but then decreased gradually to the control value after induced hypotension. Left ventricular stroke work index (LVSWI) and pulmonary vascular resistant (PVR) were unchanged from the control value during and after induced hypotension. The data indicate that nicardipine is a potent systemic vasodilator with hyperdynamic hemodynamic effects in addition to significant increase in right ventricular function.
Animals↗
[The effect of CO2 absorbent shape on its functioning time].
A comparative investigation into the functioning time of three brands of CO2 absorbents was performed. The three investigated brands were: Viosorb, Wakolime, and Wakolime-A. In this study PICO2 was measured to know the drug's functioning time and CO2 elimination from the model lung fixed at 200 or 300 ml.min-1. PICO2 was less than 1 mmHg for 34 to 55 hours at VCO2 of 200 ml. min-1 and for 32 to 48 hours at VCO2 of 300 ml.min-1. PICO2 increased exponentially in all CO2 absorbents. There were statistically significant relation between PICO2 and time. The CO2 absorbent whose shape is tablet has the longest functioning time because it could be placed smoothly in the canister. It is concluded that the shape of CO2 absorbent plays a role in determining its functioning time.
Absorption↗
[Endocrine effects of hypotension induced by nicardipine in rabbits].
Endocrine effects of hypotension induced by nicardipine, a calcium antagonist, were studied in 18 male rabbits under halothane anesthesia. They were randomly divided into two groups; nicardipine (group N; n = 10) and controls (group C; n = 8). No change was noted in plasma catecholamines in group C throughout the experiment, but plasma renin activity decreased progressively. During and after induced hypotension, in group N, plasma epinephrine was significantly higher than the control value. The highest level of plasma epinephrine was seven times of the control value during 30 minutes after induction of hypotension. Plasma norepinephrine of group N was significantly higher than the controls. The maximum increase occurred 60 minutes after induction of hypotension. Plasma renin activity of group N was significantly higher than the control value. Compared with the control value (15.1 +/- 1.8 ng.ml-1.hr-1), plasma renin activity was activated 30 and 60 minutes after induction of hypotension (55.5 +/- 6.0 ng.ml-1.hr-1, P less than 0.001, 50.3 +/- 7.1 ng.ml-1.hr-1, P less than 0.01, respectively). In conclusion, our data show that hypotension by nicardipine activates the renin-angiotensin-sympathetic system.
Animals↗
[Plasma and red blood cell cyanide concentrations during hypotension induced by sodium nitroprusside or by a nitroprusside-trimetaphan mixture in rabbits].
Plasma and red blood cells cyanide concentrations during hypotension induced by sodium nitroprusside and a nitroprusside-trimetaphan mixture were studied in 29 male rabbits under halothane anesthesia. They were randomly divided into three groups; Nitroprusside (group N; n = 10), A nitroprusside-trimetaphan mixture (group M; n = 10), Controls (group C; n = 9). No changes were noted in plasma and red blood cells cyanide concentrations in group C throughout the experiment. During and after induced hypotension, in group N, plasma cyanide concentration was significantly higher than the control value. The maximum increase occurred 60min after induction of hypotension and the highest concentration of plasma cyanide was six times the control value. In contrast, in group M, plasma cyanide concentration was unchanged from the control value. However, during and after induced hypotension, red blood cells cyanide concentrations of group N and group M were significantly higher compared with the control values. Red blood cells concentrations of cyanide increased for 30 and 60 min during induced hypotension in group N (27.11 +/- 3.9 micrograms.ml-1, P less than 0.001, 46, 73 +/- 4.7 micrograms.ml-1, P less than 0.001, respectively) and in group M (0.31 +/- 0.05 micrograms.ml-1, P less than 0.05, 0.29 +/- 0.03 micrograms.ml-1, P less than 0.05, respectively). In conclusion, the data suggest that a nitroprusside-trimetaphan mixture is a safe method for hypotensive anesthesia.
Animals↗
[Reparative effects of sodium alginate (Alloid G) on radiation stomatitis].
Discontinuation or alteration of the schedule of radiation therapy is often necessary in patients with tumors of the parotid gland and pharynx because of the development of stomatitis. Alloid G (Sodium alginate; AL-G) is an agent with a promotive effect on healing of inflammation of the gastric and esophageal mucosa. In this study, we orally administered the agent in irradiated mice to examine its healing effect against radiation stomatitis. ICR mice (5-week-old males) were subjected to gamma-irradiation at 17-32 Gy, and followed by oral administration with either AL-G, polyvinyl pyrrolidone (PVP), or water twice daily for 20 days. The effects of the treatments on radiation stomatitis were examined according to the survival of the animals and histological findings in the oral mucosa. After irradiation at 32 Gy, it was found that the epidermal basal layer was present in the AL-G group. In both PVP and water-treated groups, however, it was not found. The dose modification factor (DMF) of 1.12 was calculated from oral radiation death of LD50/20 and radiation dose with or without AL-G. These results suggest that AL-G probably have a pharmacologically reparative effect on radiation injury of the oral mucosa, in addition to the physical epidermal protective effect due to its viscosity such as that of PVP.
Administration, Oral↗
A collagen-binding glycoprotein from bovine platelets is identical to propolypeptide of von Willebrand factor.
Several proteins from bovine platelet lysate bound to type I collagen immobilized to the beads of formyl derivatives of cellulose. Among these proteins, a protein of about 100,000 daltons was purified to homogeneity by two additional affinity chromatographies, an organomercurial-agarose and a lentil lectin-agarose. This protein consisted of a single polypeptide chain which contains carbohydrate moiety and many intrapolypeptide disulfide bridges. In addition to platelets, this protein was present in plasma and cultured endothelial cells but not in red blood cells, leukocytes, and smooth muscle cells. Furthermore, it was released from platelets upon stimulation by various agonists. The purified 100-kDa protein was labeled with 125I to quantitate its binding to fibrillar type I collagen. The protein specifically bound to fibrillar collagen with the apparent dissociation constant of 5.6 x 10(-8) M for the high affinity site and 5.5 x 10(-7) M for the low affinity site. Analyses of amino acid sequences of both intact and tryptic fragments of this protein revealed that it had strong homology to the propolypeptide of human von Willebrand factor, which is also known as von Willebrand antigen II. Various properties of this protein listed above also strongly suggest that it was indeed the propolypeptide of bovine von Willebrand factor.
Amino Acid Sequence↗
Inhibition of platelet-collagen interaction by propolypeptide of von Willebrand factor.
A collagen-binding glycoprotein was isolated from human platelets using affinity chromatography of immobilized collagen. Based upon characterizations of this protein we confirmed that it was identical to the propolypeptide of von Willebrand factor (pp-vWF), which is also called von Willebrand antigen II. The characteristics we have investigated are molecular weight, existence of carbohydrate chains, and the NH2-terminal amino acid sequence. pp-vWF has strong affinity to collagen and inhibits collagen-induced aggregation of human platelets at a concentration as low as 2 micrograms/ml even in the presence of plasma. This inhibitory effect is specific for collagen-induced aggregation since it does not inhibit aggregation of platelets induced by other agonists such as ADP, arachidonic acid, platelet-activating factor, ionophore A23187, and ristocetin. As pp-vWF is quickly released from platelets upon activation by various agonists, it is possible that pp-vWF functions as a repressor for excess platelet aggregation induced by collagen and constitutes a negative feed-back mechanism. Considering the fact that mature vWF supports platelet adhesion to subendothelium, present observations suggest that the propeptide portion and the mature protein could have opposing effects on hemostasis.
Amino Acid Sequence↗
Enhancement of plasminogen activator activity in cultured endothelial cells by granulocyte colony-stimulating factor.
A hitherto unknown function of granulocyte colony-stimulating factor (G-CSF) was found using cultured endothelial cells. G-CSF stimulated activity of plasminogen activator (PA) in both extracellular and intracellular milieus of endothelial cells obtained from bovine carotid and aortic artery. This effect was dependent on the concentration of G-CSF added to the culture medium and on the treatment time. The extracellular activity was enhanced approximately 5-fold at a concentration of 5,000 colony-forming unit (CFU)/ml (2.6 nM) and in about a 15-hr treatment period. Analyses by fibrin and reverse fibrin autography revealed that activity of PA was much more increased than that of PA inhibitor in endothelial cells treated with G-CSF.
Animals↗
Treatment of skin and median nerve defects with peroneal neurofasciocutaneous flap.
A large neurofasciocutaneous flap that consisted of a peroneal flap and a segment of sural nerve was used in the simultaneous reconstruction of a large soft tissue and nerve defect caused by a crushing injury of the distal forearm. A 10 x 15 cm peroneal flap, including a 10 cm segment of sural nerve, was successfully transferred to an 8 x 12 cm skin defect, reconstructing a 5 cm defect of the median nerve. Two years after repair, the opponens pollicis muscle showed good contraction, although palmar abduction of the thumb remained poor. Static two-point discrimination was 20 mm on the pulp surface of both thumb and index finger and 15 mm on the middle finger.
Adult↗
Continuous local intra-arterial infusion of anticoagulants for digit replantation and treatment of damaged arteries.
From May 1958 to May 1987, 428 upper extremities were replanted, with an overall survival rate of 87.4 percent. With the aim of increasing the survival rate a new method was tried. Unlike conventional continuous intravenous infusion, a Teflon catheter (28 gauge) was inserted into the proximal main artery of the anastomosed artery, and a daily dose of 80 ml comprising 240,000 U of urokinase, 40 micrograms of prostaglandin E1, 10,000 U (maximum) of heparin, and low molecular weight dextran was administered by means of continuous infusion for the 10 consecutive days, during which arterial thrombosis is likely to occur. Thirteen cases (replantations and damaged digital arteries) survived without any re-operation for arterial thrombus. There were statistically significant differences (p less than 0.025) in platelet count, fibrinogen, and AT III preoperatively and three days postoperatively. There were also statistically significant differences (p less than 0.05) in prothrombin time, partial thromboplastin time, and clotting time between pre-operative measurements and those taken four and 15 hr postoperative, but those data remained within normal range. No abnormalities were present in the arteries through which the catheter was inserted, as validated by postoperative digital subtraction angiography.
Adult↗
Pedicled and "flow-through" venous flaps: clinical applications.
Recently, the pedicled venous flap and "flow-through" venous flap have been the focus of increasing attention for skin defects of the fingers and hands. For successful venous flap use, the following approaches have been suggested: (1) a pedicled venous flap with preservation of the draining veins alone; (2) a "flow-through" flap with preservation of a flow-through vein in the flap; and (3) an arterialized "flow-through" venous flap which ensures arterial blood flow into the flap. Based on findings that venous blood is helpful in flap survival, the authors made use of the first two flap types, the pedicled venous flap and the "flow-through" venous flap and attempted to establish and clarify reasonable conditions for flap survival. Venous pressure of the finger and elbow was measured and venographies of the finger and hand were also carried out. The following conditions are regarded as essential in successful venous flap procedures: (a) use of a venous flap with a rich venous network; (b) preservation of many "flow-through" veins; (c) harvesting a pedicled venous flap where the veins have afferent (reversed) venous pressure; and (d) anastomosing veins of the "flow-through" flap with recipient veins where high efferent venous pressure exists and differential pressure is observed. Clinical cases are presented and the authors attempt to explain flap failure from previously unknown causes. Conditions for flap harvesting are also discussed.
Adult↗
Experimental studies of skin flaps with subcutaneous veins.
The authors have previously reported that skin flaps with subcutaneous veins nourished by arterial or venous inflow survived, despite being sited on recipient beds with poor circulation. In these previous studies, experimental models were based on axial pattern flaps of rabbit ears. However, for clinical application, there are problems in the use of axial pattern flaps with central vessels. This report classifies skin flaps with subcutaneous veins and produces experimental models that are suitable for clinical application and investigation of survival rates. Thirty-seven rabbits (74 ears) were used in this study. A 3.0-cm x 4.5-cm skin flap with only a "passing" vein (one that traveled through the tissue without major branches to that tissue) was raised at the level of the perichondrium on the dorsum of the auricular cartilage. The flaps were divided into three groups: Group A--composite flaps (n = 10); Group B--totally venous perfused flaps (n = 30); and Group C--afferent arterialized venous perfused flaps (n = 34). More than 80 percent of the flaps became necrotic in Group A. In Group B, 18 of 20 survived with partial superficial necrosis and two became more necrotic. In Group C, 18 of 21 flaps survived with superficial necrosis and three became more necrotic. Microangiographically, as concerns the "passing" veins in Groups B and C flaps, all of the flaps survived with only superficial necrosis. The skin flaps with subcutaneous veins survived as total venous perfusion flaps (TVPF) and as arterialized afferent venous perfusion flaps (AAVPF) even though the artery was not included in the flap. The experimental model is suitable for the investigation of the clinically unconventional flap.
Animals↗